Non insulin diabetes mellitus (NIDDM) is a clinically heterogeneous disorder (Kahn, C. R. (1994) Diabetes 43:1066-1084) characterized by insulin resistance in peripheral tissues combined with impaired insulin secretion of the pancreatic .beta.-cell (DeFronzo, R. A. et al. (1992) Diabetes Care 15:318-368). Investigations of candidate genes for NIDDM have led to the identification of polymorphisms of several genes encoding proteins of insulin action and insulin secretion, but none show a high frequency of association with the disease (Kahn, C. R. et al. (1996) Annu. Rev. Med. 47:509-531; McCarthy, M. I. et al. (1994) Diabetologia 37:959-968).
Friedreich's ataxia (FRDA) is the most common hereditary ataxia (Campuzano, V. et al. (1996) Science 271:1423-1427), with an estimated prevalence of 1 in 50,000 people (Epplen, C. et al. (1997) Hum. Genet. 99:834-836). FRDA is a degenerative disease characterized by progressive ataxia, lack of tendon reflexes, loss of position sense, dysarthria, and hypertrophic cardiomyopathy. FRDA is inherited as an autosomal recessive disease. FRDA appears to belong to the family of triplet repeat disorders, including myotonic dystrophy, fragile X syndrome, and Huntington's disease (Wells, R. D. (1996) J. Biol. Chem. 271:2875-2878). The FRDA has been mapped to chromosome 9q13-q21 (Hanauer, A. et al. (1990) Am. J. Hum. Genet. 46:133-137) and attributed to a GAA triplet repeat expansion (McCarthy, M. I. et al. (1994) Diabetologia 37:959-968) in the frataxin gene, also known as X25 or STM7. Frataxin encodes a protein, which is targeted to the mitochondria and has been suggested to function as an endogenous antioxidant (Rotig, A. et al. (1997) Nat. Genet. 17:215-217).